Beguiling Badass B Cells Flashcards
1
Q
Rich Diversity of B cells stems from:
A
combinational diversity, junctional diversity, N & P nucleotides, somatic mutation
2
Q
The Memory of B cells stems from:
A
somatic mutation and clonal selection of Fab, Ig heavy chain class switching of Fc, rapid response
3
Q
CD79
A
(aka Igalphabeta), has ITAM, transmits signals from the BCR to the B-cell, is functional in the pre-B cell
4
Q
3 molecules unique to the B cell
A
CD19, CD20, CD22
5
Q
hematopoietic stem cells
A
B cell progenitor
6
Q
first stage with specific B cell markers
A
Pro-B
7
Q
first stage with a rearranged heavy chain
A
Pre-B
8
Q
first stage with a functional BCR
A
immature B cell
9
Q
where does final B cell maturation occur?
A
in the periphery
10
Q
where does B cell development occur in the fetus
A
the fetal liver (pre-B cells appear at the end of the first trimester; by the second trimester, B cell differentiation occurs in the bone marrow, in the newborn >50% of B cells have CD5)
11
Q
Characteristics of the stem cell B cell
A
no B cell specific markers, express CD34
12
Q
characteristics of the Pro-B cell
A
B cell specific CD19, IL-7 dependent growth, heavy chain rearrangement
13
Q
characteristics of the Pre-B cell
A
express pre-BCR, have rearranged heavy chain and surrogate light chain, signals via CD79, also has CD20 and IL-7R (still)
14
Q
characteristics of the immature B cell
A
the first stage when the B cell can “sense” the antigenic milieu, B-cell tolerance occurs at this stage, expressed mIgM, CD19, CD20, Cd21, CD22, CD79
15
Q
characteristics of the mature B cell
A
IgM and IgD, CD19, CD20, CD21, CD22, CD79
16
Q
IL-7R
A
found only on the pro-B cell and the pre-B cell
17
Q
IgD is found at what stage(s) of B cell development?
A
mature B cell
18
Q
surrogate light chain
A
found on pre-B cells, is non-variant, is composed of VpreB and λ5
19
Q
λ5
A
indicative of the pre-B cell
20
Q
stage at which B cell tolerance occurs
A
immature B cell stage (must have fully formed BCR)
21
Q
2 criteria the immature B cell is tested for
A
- productivity 2. self-reactivity
22
Q
3 mechanisms of b cell tolerance (negative selection)
A
- B-cell receptor editing; 2. deletion; 3. anergy
23
Q
BCR editing
A
occurs through the secondary VJ rearrangement at the Ig-light chain locus - accomplished via RAG enzymes (2-3 attempts)
24
Q
deletion via apoptosis
A
death to B cells that are strongly reactive to self antigens of reactive to membrane bound antigens
25
anergy
is functional paralysis, occurs to B cells that are weakly reactive to self antigens or are reactive soluble antigens. Anergic B cells can exit to the periphery (but die quicker and respond poorly)
26
alternative B cell RNA splicing
allows co-expression of δ and μ heavy chains (μ is first on the RNA and δ is second)
27
products of peripheral B cell development
memory B-cells and plasma cells
28
total circuit time of B cells
12-24 hours
29
B cells that never meet their cognate antigen
usually die within B cell follicles
30
the spleen
monitors for blood borne pathogens
31
lymph nodes
monitor tissue-derived pathogens
32
MALT
monitors for pathogens entering via the mucosal portal
33
GALT
monitors for enteric pathogens (including Peyer's patches)
34
WBC count
4,000-11,000 WBC/μl
35
lymphocyte count
1,000-4,000 lymphocytes/μl (15-40% of WBC)
36
secondary lymphoid organ T:B cell ratio
is generally 2:1 (T:B) -- except the spleen that has more B cells than T cells
37
TDL
thoracic duct lymph - joins the blood before it recirculates to the heart; connects the lymphatic and blood circulations
38
L-selectin
CD62L only expressed by naive lymphocytes, interacts with GlyCAM1 (found on HEV); allows lymphocytes to enter lymph nodes form the blood, down regulated in activated effector lymphocytes
39
LFA1, VLA4, CD
bind to ICAM1, VCAM1, and LFA3 respectively; allow effector lymphocytes to enter inflamed tissues; VCAM is the most important for this extravasation process
40
difference between a primary and secondary follicle
a secondary follicle has a germinal center
41
Lymph Node vs. Spleen: T cell location
paracortex; PALS
42
Lymph Node vs. Spleen: naive B&T cell point of entry
HEV; central arteriole
43
white pulp
both B and T cell zones
44
Lymph Node vs. Spleen: macrophages and plasma cells
medullary cords; red pulp
45
Lymph Node vs. Spleen: marginal zone macrophages and marginal zone B-cells
sub-capsular sinus; marginal sinus -- --- important for T independent immune responses
46
sub-capsular/marginal sinus power
have B cells that an "sense" pathogens as they enter the spleen or lymph nodes
47
general lymphatic flow
afferent lymphatics --> sub-capsular sinus --> cortical sinus --> medullary cords --> efferent lymphatics
48
Activation of B cells requires how many triggers, and what are they
2 triggers: 1. antigen binding to the BCR; 2. helper T cells through CD40 (antigen specific, LINKED RECOGNITION) *a third cytokine based signal is helpful, but not necessary
49
why is the necessary T/B cell interaction for B cell activation relevant?
it ensures that both B and T cells must be activated in order to create a response which decreases the likelihood of autoimmunity; "when self-tolerance is breached in both B and T cells"
50
stopping of antigen specific lymphocytes occurs
in the T-cell zone
51
linked recognition
does not require the T and B cell to bind to the same epitope on the antigen
52
What happens after the B cell is activated by an antigen
1. the B cell processes the antigen and presents it on an MHC Class II molecule; 2. the B cell up regulates CD40 and CD80/CD86; 3. the B cell presents this antigen to a T cell 4. the B cell CD80/CD86 (B7-1/B7-2) parley with CD28 (this causes CD40L to be up regulated on the T cell) 4. the B cell CD40 parleys with recently up regulated CD40L 5. ACTIVATION
53
T cells in the T cell zone
are likely activated by antigens presented by dendritic cells, not B cells
54
Fate of B cells activated in the T-cell zone
1. form a primary focus, maturate into plasma cells, secrete antibodies; 2. travel to B-cell follicles, create a germinal center (guided by chemokines)
55
somatic mutation
"random insertions of mutations in the hypervariable regions of the Ig", occurs after antigen stimulation, key enzyme is AID
56
germinal center, dark zone
where somatic mutation occurs --> creates a "panel of clonal offspring" with a "wide range of affinities for the antigen"
57
affinity maturation
say yes to the antigen: B-cell style; occurs via somatic mutation and subsequent positive selection of b cell clones
58
germinal center, light zone
contains follicular dendritic cells (DC with lots of antigen and immune complexes), where B-cell clone positive selection occurs
59
what cells help B cells isotype switch from IgM
T follicular helper cells (mediated by AID, CD40L, and cytokines)
60
AID
critical for B cell class switching and somatic mutation (same thing?? ask)
61
plasma cell home, short term and long term
short: medullary cords and red pulp, long term: bone marrow (account for most of serum Ig
62
memory B cells
class switched, lack IgD, higher affinity for antigens, lower threshold for activation, are in Go state, reside in the sub-capsular sinus and in the marginal sinus, can traffic to inflamed tissues, some are found in B-cell follicles
63
IgD
not found on memory B cells
64
the m in mIgM
"membrane", as in membrane bound
65
class switching is mediated by
the switch region at the 5' end of each constant heavy chain gene (also is unique to heavy chains!)
66
class switching occurs at what level and where
occurs at the DNA level and only one ONE chromosome (mediated by cytokines and AID)
67
cytokines in class switching
determine which switch regions will rearrange - switching is irreversible, the VDJ region is upstream of the 2 switch regions and the intended constant heavy chain region
68
IgA
T-reg, TGFβ; TH2, IL-5
69
IgE
TH2, IL-4/IL-13
70
IgG(1)
TH1, IFN-γ
71
IL-6
drives plasma cells
72
IL-2, IL-4
cytokines that act as the third "signal" for B cells
73
primary immune response: IgM
peaks first, clinically indicates a recent infection (if high relative to IgG); increase in IgM occurs as a result of naive cell activation, IgM appears at 7 days, peaks at 10 days, and returns to baseline at 14 days
74
primary immune response: IgG
peaks after IgM, is produced by a "minor subset of plasma cells" that switch from IgM secretion to IgG secretion
75
secondary immune response: IgG
from the memory B-cells with high affinity IgG BCRs, IgG > IgM, immune response is quicker and stronger
76
primary immune response
orchestrated in the T-cell zone
77
three products of a successful secondary immune response
1. effector T cells; 2. memory T/B cells 3. plasma cells and antibodies
78
memory B-cells and germinal centers
some memory B-cells can generate new germinal centers (can produce further affinity maturation)
79
the best antigens are in what form and why
those that are aggregated and/or presented in native (multivalent array) form; this is true because in order to activate a BCR, two or more IgM/D molecules must be "cross-linked to the antigen"
80
CD73
is like CD3 on T cells; BCR activation (x-linking!) --> CD79 chain ITAMs (Ig-α, Ig-β) are phosphorylated --> recruit the tyrosine kinase 'Syk' --> causes phosphorylation of BTK --> activation of PLCγ2 --> DAG, IP3 --> NFAT, PKC, calcium, calcineurin, NFAT/PKC, NFκB/MAP kinase
81
C3d
binds to CD21 (i.e. CR2) --> CD19 --> Fyn/Lyn;Vav/Pl-3K --> augmentation of B-cell signal 1
82
antigen-antibody immune complex feedback
dampens B-cell signal via CD32 (FcRγIIb) --> phosphatase activation
83
CD22
feedback pathway B-cell receptor: down regulates B-cell signaling
84
CD32
FcRγIIb: low affinity Fc receptor
85
CD81
something, something, amplification of BCR signal
86
CD20
something, something, amplification of BCR signal
87
CD40L is also known as
CD154 (this is a T-cell receptor)
88
TI antigens
t-cell independent antigens
89
T-cell dependent responses are characterized by what three things?
1. class switching, 2. affinity maturation, 3. memory
90
TI-1 ligands
act as a mitogen, trigger ALL B-cells polyclonally (ex - LPS); work via a toll like receptor, turn the B cell into a IgM warehouse
91
TI-2 ligands
cross-link a large amount of BCRs, are polymeric antigens (ex. flagellin, Ficoll, dextran, bacterial polysaccharides); good at activating 'primitive B cells' (B-1 B cells -- CD5) and marginal zone B cells
92
mitogen
"a chemical substance that encourages a cell to commence cell division", "Mitogenesis is the induction (triggering) of mitosis, typically via a mitogen"
93
B-1 B cells
primitive B cells located in the peritoneal and pleural cavities, express the surface marker CD5
94
TI antigens
do not create a response that has class switching, affinity maturation, or memory
95
marginal zone B cells
are necessary to fight TI-2 antigens!
96
allotypes
different members of a species will differ with one another with respect to which particular alleles of a given isotype they received from their parents
97
T or F: different idiotypes can be detected in the sera
False - they have too low of a frequency (exceptions - patients with clonal expansion and mice with BCR transgenic B-cells
98
antibody with the longest half life
IgG - 23 days
99
antibody that can cross the placenta
IgG
100
antibody that binds FcR
IgG (and IgA, weakly)
101
antibody that can induce ADCC
IgG
102
antibody that can neutralize toxin
IgG
103
antibody found in milk
IgG, IgA
104
antibody with anti-viral activity
IgG, IgA
105
antibody with anti-bacterial properties
IgG, IgA (think lysosomes)
106
antibodies that are agglutinators (best to worst)
IgM, IgA, IgG
107
antibodies that fix complements
IgM and IgG (much less than IgM)
108
antibodies with the highest and lowest molecular weights
IgM (900,000 Da), IgG (150,000 Da)
109
antibodies with J and/or S chains
IgA (J and S), IgM (J)
110
antibody found in secretions
IgA (also is intravascular)
111
where is IgG found
intravascular and extravascular
112
where is IgM found
mostly intravascularly
113
IgG is good at
neutralizing toxins and viruses (blocking binding) and opsonization
114
macrophages have receptors for
Fc (Fc receptor) and C3b (CR1)
115
ADCC
via IgG binding to FcR on macrophages, basophils, NK cells, and eosinophils
116
the first Ig a newborn makes
IgM (plateaus at 1-2 yrs.)
117
IgA dimerization
increases its avidity --> powerful at neutralizing toxins (but doesn't bind complement, does not do ADCC)
118
know which cell produces Ig-h, Ig-κ, J-chain, and Poly-Ig receptor chains
huh, wtf? ask, poly Ig is from epithelial cells, j chain is from plasma cells, Ig-h & Ig-κ in plasma cell
